Imidazothiazines, derivatives and analogues thereof

Abstract

Disclosed are 2,3,5,6-tetrahydro-8H-imidazo-[2,1-c][1,4]thiazines, analogues and derivatives thereof which are effective in inhibiting indoleamine-N-methyl transferase and thus useful in the treatment of mental aberrations, such as schizophrenia. Also disclosed are processes for the preparation of such imidazothiazines; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions.

What is claimed is: 
     
       1. A compound having the structure: ##SPC5## wherein A is selected from the group consisting of S, O, and NR; and wherein R is selected from the group consisting of hydrogen, lower alkyl, or lower alkoxycarbonyl; and R 1  and R 2  are independently selected from the group consisting of hydrogen, halogen, lower alkyl, and lower alkoxy carbonyl; and the pharmaceutically acceptable N-acid addition salts thereof.   
     
     
       2. A compound according to claim 1 which is 2,3,5,6-tetrahydro-8H-imidazo[2,1-c] [1,4]-thiazine. 
     
     
       3. A compound according to claim 1 which is 2,3,5,6-tetrahydro-8H-imidazo[2,1-c] [1,4]-oxazine. 
     
     
       4. A compound according to claim 1 which is ethyl 2,3,5,6,7,8-hexahydroimidazo[1,2-a] -pyrazine-7-carboxylate. 
     
     
       5. A process for preparing a compound having the structure: ##SPC6## thereof which comprises cyclizing in the presence of base a compound having the structure: ##SPC7##   wherein X is halogen;   A is selected from the group consisting of S, O, NR;   R 1  and R 2  are independently selected from the group consisting of hydrogen, halogen, lower alkyl, or lower alkoxy carbonyl; and R is selected from the group consisting of hydrogen, lower alkyl, and lower alkoxycarbonyl.   
     
     
       6. A pharmaceutical composition comprising a therapeutically effective amount in unitary dosage form of a compound having the structure: ##SPC8## wherein A is selected from the group consisting of S, O, and NR; and wherein R is selected from the group consisting of hydrogen, lower alkyl, or lower alkoxy carbonyl; and R 1  and R 2  are independently selected from the group consisting of hydrogen, halogen, lower alkyl, and lower alkoxycarbonyl; and the pharmaceutically acceptable N-acid addition salts thereof; and a pharmaceutical carrier therefor.   
     
     
       7. A method of treatment comprising administering a therapeutically effective amount in unitary dosage form of a compound having the structure: ##SPC9## wherein A is selected from the group consisting of S, O, and NR; and wherein R is selected from the group consisting of hydrogen, lower alkyl, or lower alkoxy carbonyl; and R 1  and R 2  are independently selected from the group consisting of hydrogen, halogen, lower alkyl, and lower alkoxycarbonyl; and the pharmaceutically acceptable N-acid addition salts thereof.